Wadei, Hani M.

AbstractBackgroundHistologic acute graft pyelonephritis (HAGPN) after kidney transplantation (KT) has been assessed less frequently than urinary tract infections (UTIs) or clinical acute graft pyelonephritis. Risk factors for HAGPN, its association with graft loss, and measures that might prevent it are not known.MethodsWe performed a retrospective review of HAGPN cases identified from KT occurring between January 2008 and December 2017 at our institution. We compared the HAGPN cases to a randomly selected control group of KTs to identify risk factors using univariate and multivariate Cox regression models. The association between HAGPN and graft loss was also assessed, similarly.ResultsHAGPN was identified in 46 of 1391 patients (cumulative incidence, 5% [95% CI, 3%–7%]) undergoing KT at a single center from January 2008 through December 2017 (median time to diagnosis, 241 days after KT; interquartile range, 122–755 days). Indications for biopsy were follow‐up of treated rejection (n = 20 [43%]), KT protocol biopsy (n = 19 [41%]), and acute kidney injury (n = 7 [15%]). Histologic rejection, UTI, and asymptomatic bacteriuria (ASB) were present in 23 (50%), 9 (20%), and 16 (35%). Multivariate Cox proportional hazards models comparing KT recipients with or without HAGPN (n = 46 and n = 138, respectively) showed that HAGPN was associated with urologic complication by day 30, delayed graft function, previous UTI or ASB, and a history of rejection. In the univariate and multivariate analyses, HAGPN was associated with an increased risk of graft loss.ConclusionHAGPN is an infrequent, unanticipated, and clinically significant complication of KT.

Background. Improving both patient and graft survival after kidney transplantation are major unmet needs. The goal of this study was to assess risk factors for specific causes of graft loss to determine to what extent patients who develop either death with a functioning graft (DWFG) or graft failure (GF) have similar baseline risk factors for graft loss. Methods. We retrospectively studied all solitary renal transplants performed between January 1, 2006, and December 31, 2018, at 3 centers and determined the specific causes of DWFG and GF. We examined outcomes in different subgroups using competing risk estimates and cause-specific Cox models. Results. Of the 5752 kidney transplants, graft loss occurred in 21.6% (1244) patients, including 12.0% (691) DWFG and 9.6% (553) GF. DWFG was most commonly due to malignancy (20.0%), infection (19.7%), cardiac disease (12.6%) with risk factors of older age and pretransplant dialysis, and diabetes as the cause of renal failure. For GF, alloimmunity (38.7%), glomerular diseases (18.6%), and tubular injury (13.9%) were the major causes. Competing risk incidence models identified diabetes and older recipients with higher rates of both DWFG and nonalloimmune GF. Conclusions. These data suggest that at baseline, 2 distinct populations can be identified who are at high risk for renal allograft loss: a younger, nondiabetic patient group who develops GF due to alloimmunity and an older, more commonly diabetic population who develops DWFG and GF due to a mixture of causes—many nonalloimmune. Individualized management is needed to improve long-term renal allograft survival in the latter group.

Abstract We characterized coronavirus disease 2019 (COVID-19) breakthrough cases admitted to a single center in Florida. With the emergence of delta variant, an increased number of hospitalizations was seen due to breakthrough infections. These patients were older and more likely to have comorbidities. Preventive measures should be maintained even after vaccination.

INTRODUCTION: Urinary neutrophil gelatinase-associated lipocalin (NGAL) has shown promise in differentiating acute tubular necrosis (ATN) from other types of acute kidney injuries (AKIs) in cirrhosis, particularly hepatorenal syndrome (HRS). However, NGAL is not currently available in clinical practice in North America. METHODS: Urinary NGAL was measured in a prospective cohort of 213 US hospitalized patients with decompensated cirrhosis (161 with AKI and 52 reference patients without AKI). NGAL was assessed for its ability to discriminate ATN from non-ATN AKI and to predict 90-day outcomes. RESULTS: Among patients with AKI, 57 (35%) had prerenal AKI, 55 (34%) had HRS, and 49 (30%) had ATN, with a median serum creatinine of 2.0 (interquartile range 1.5, 3.0) mg/dL at enrollment. At an optimal cutpoint of 244 μg/g creatinine, NGAL distinguished ATN (344 [132, 1,429] μg/g creatinine) from prerenal AKI (45 [0, 154] μg/g) or HRS (110 [50, 393] μg/g; P < 0.001), with a C statistic of 0.762 (95% confidence interval 0.682, 0.842). By 90 days, 71 of 213 patients (33%) died. Higher median NGAL was associated with death (159 [50, 865] vs 58 [0, 191] μg/g; P < 0.001). In adjusted and unadjusted analysis, NGAL significantly predicted 90-day transplant-free survival ( P < 0.05 for all Cox models) and outperformed Model for End-Stage Liver Disease score by C statistic (0.697 vs 0.686; P = 0.04), net reclassification index (37%; P = 0.008), and integrated discrimination increment (2.7%; P = 0.02). DISCUSSION: NGAL differentiates the type of AKI in cirrhosis and may improve prediction of mortality; therefore, it holds potential to affect management of AKI in cirrhosis.

Acute kidney injury (AKI) in the setting of cirrhosis (hepatorenal syndrome [HRS]–AKI) is a severe and often fatal complication of end‐stage liver disease. The goals of treatment are to reverse renal failure and prolong survival in patients who are critically ill. However, interventions have limited efficacy, and mortality rates remain high. In the United States, the mainstay of pharmacologic therapy consists of the off‐label use of vasoconstrictive agents in combination with plasma expanders, a strategy that produces modest effects. Liver transplantation is the ultimate solution but is only an option in a minority of patients because contraindications to transplantation are common and organ availability is limited. Renal replacement therapy is a temporary option but is known to confer an extremely poor short‐term prognosis in patients with HRS‐AKI and at best serves as a bridge to liver transplantation for the minority of patients who are transplantation candidates. The high mortality rate associated with HRS‐AKI in the United States is a reflection of the suboptimal standard of care. Improved therapeutic options to treat HRS‐AKI are sought. Terlipressin is a drug approved in Europe for treatment of HRS‐AKI and supported by recommendations for first‐line therapy by some liver societies and experts around the world. This review article will discuss the substantial unmet medical need associated with HRS‐AKI and the potential benefits if terlipressin was approved in the United States.

Abstract Hepatorenal syndrome (HRS) is a functional renal failure that develops in patients with advanced hepatic cirrhosis with ascites and in those with fulminant hepatic failure. The prevalence of HRS varies among studies but in general it is the third most common cause of acute kidney injury (AKI) in cirrhotic patients after pre-renal azotemia and acute tubular necrosis. HRS carries a grim prognosis with a mortality rate approaching 90% three months after disease diagnosis. Fortunately, different strategies have been proven to be successful in preventing HRS. Although treatment options are available, they are not universally effective in restoring renal function but they might prolong survival long enough for liver transplantation, which is the ultimate treatment. Much has been learned in the last two decades regarding the pathophysiology and management of this disease which lead to notable evolution in the HRS definition and better understanding on how best to manage HRS patients. In the current review, we will summarize the recent advancement in epidemiology, pathophysiology, and management of HRS.

Renal vein thrombosis is a rare, but potentially serious complication in patients with renal transplantation as it can lead to non-reversible graft injury and failure. Often this clinical entity is found in the early transplantation period, and the available management strategies are associated with favourable patient outcomes. The incidence, pathophysiology and outcomes for the delayed occurrence of renal vein thrombosis are unknown. The case here describes a unique situation with an excellent clinical outcome related to early diagnosis and appropriate care.

Pre–liver transplantation (LT) renal dysfunction is associated with poor post‐LT survival. We studied whether early allograft dysfunction (EAD) modifies this association. Data on 2,856 primary LT recipients who received a transplant between 1998 and 2018 were retrospectively reviewed. Patients who died within the first post‐LT week or received multiorgan transplants and previous LT recipients were excluded. EAD was defined as (1) total bilirubin ≥ 10 mg/dL on postoperative day (POD) 7, (2) international normalized ratio ≥1.6 on POD 7, and/or (3) alanine aminotransferase or aspartate aminotransferase ≥2000 IU/mL in the first postoperative week. Pre‐LT renal dysfunction was defined as serum creatinine >1.5 mg/dL or on renal replacement therapy at LT. Patients were divided into 4 groups according to pre‐LT renal dysfunction and post‐LT EAD development. Recipients who had both pre‐LT renal dysfunction and post‐LT EAD had the worst unadjusted 1‐year, 3‐year, and 5‐year post‐LT patient and graft survival, whereas patients who had neither renal dysfunction nor EAD had the best survival (P < 0.001). After adjusting for multiple factors, the risk of death was significantly higher only in those with both pre‐LT renal dysfunction and post‐LT EAD (adjusted hazard ratio [aHR], 2.19; 95% confidence interval [CI], 1.58‐3.03; P < 0.001), whereas those with renal dysfunction and no EAD had a comparable risk of death to those with normal kidney function at LT (aHR, 1.12; 95% CI, 0.86‐1.45; P = 0.41). Results remained unchanged when pre‐LT renal dysfunction was redefined using different glomerular filtration rate cutoffs. Pre‐LT renal dysfunction negatively impacts post‐LT survival only in patients who develop EAD. Livers at higher risk of post‐LT EAD should be used with caution in recipients with pre‐LT renal dysfunction.

Abstract Background Histologic acute graft pyelonephritis (HAGPN) is a complication of kidney transplantation (KT) diagnosed serendipitously by renal biopsy. A retrospective review of 1391 patients who underwent KT at our institution between 2008 and 2017 identified 46 cases (cumulative incidence 5%). Rejection was present in 50% of biopsies demonstrating HAGPN, complicating management. The aims of this study were to identify risk factors and outcomes of HAGPN. Methods Recipient, donor, operative and post-transplant characteristics of 46 cases of HAGPN and 138 controls randomly selected from the 1345 patients who underwent KT between 2008 and 2017 were assessed in univariable and multivariable Cox regression models. Associations of HAGPN with death or graft failure were assessed in univariable models. Results In univariable analysis, characteristics associated with increased risk of HAGPN in order of decreasing hazard ratio (HR) were rejection (HR 10.82, 5.66-20.72), urinary tract infections (UTI) or asymptomatic bacteriuria (ASB) (HR 6.28, 3.43-11.50), urologic malfunction (UM) within 30 days of KT, (HR 5.34, 2.85-10.02), less than 4 matches at HLA A/B/DR loci (HR 3.74, 1.19-11.76), delayed graft function (DGF) (HR 2.1, 1.47-3.00), basiliximab induction (HR 1.59, 1.05-2.42), diabetes mellitus (DM) at KT (HR 1.52, 1.07-2.16), operative time (HR 1.11, 1.03-1.19) and cold ischemic time (CIT) (HR 1.05, 1.02-1.06). UM, rejection and UTI or ASB were the most significant risk factors based on clinical and statistical importance, and after adjusting for them, DM, transplant type, CIT, ureteral stent placement and DGF remained significant risk factors. In univariable analysis, ureteral stent placement at transplant (HR 0.60, 0.43-0.88) and living-related donor (HR 0.18, 0.04-0.78) were each associated with reduced risk of HAGPN which persisted after multivariable analysis. In univariable analysis, HAGPN was associated with death (HR 17.04, 7.93-39.31) and graft failure (HR 3.77, 1.73, 8.20). Conclusion HAGPN is an infrequent, unanticipated, clinically significant complication of renal transplantation. Post-transplant dysfunction of the allograft collection system may be a modifiable risk factor. Disclosures All Authors: No reported disclosures